M. Douglas Benson
Department of Biomedical Sciences
Member of the GSBS Faculty
3302 Gaston Ave.
Dallas, Texas 75246
Education and Post-Graduate Training
Ph.D., Biological Chemistry, University of Michigan, Ann Arbor, MI (2000)
M.S., Biological Chemistry, University of Michigan, Ann Arbor, MI (1994)
B.A., Chemistry, Cornell University, Ithaca, NY (1991)
Assistant Professor, Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry (2007-present)
Associate member, Christopher Reeve Foundation International Research Consortium on Spinal Cord Injury (2004-present)
Postdoctoral Research Fellow, Department of Developmental Biology, University of Texas Southwestern Medical Center (2001-2007)
Graduate Student Research Assistant, Department of Biological Chemistry, University of Michigan School of Medicine (1991-2000)
Teaching responsibilities include:
Biochemistry (dental hygiene)
Axons of neurons in the Central Nervous System (CNS) do not regenerate after a spinal cord injury (SCI) even though the axotomized neurons do not die. This is due, in large part, to the inhibitory nature of the CNS environment. We recently discovered that a repellant molecule called "ephrin-B3" that is required for proper corticospinal axon pathfinding during development is expressed in adult CNS myelin where it inhibits outgrowth of these same axons. This discovery demonstrates what had been widely proposed but not previously shown: that the molecular mechanisms used by the body to guide axons during embryonic development are reused to inhibit growth in the adult. We are currently investigating the signals that ephrin-B3 generates inside neurons through activation of its receptor, EphA4, to find out which of these signaling pathways overlap with those of other known inhibitory factors that also stunt axonal regrowth. We believe that the molecules involved at the intersection of these pathways may be targets for therapies aimed at inducing regeneration after SCI.
Our studies employ culture of neuronal cell lines and primary mouse neurons to explore the biochemistry and cell biology of specific signaling molecules and transcription factors. We also use genetically engineered mouse lines to model the effects of specific molecular manipulations on regeneration in experimentally induced SCI.
Role of ephrins in osteoblast differentiation. Benson MD (PI); 1 R03 DE020119-01; 2010-2011; $109,875.
Ephrin inhibition of regeneration after spinal cord injury. Benson MD (PI); Christopher and Dana Reeve Foundation; 2011-2012; $150,000.
Benson MD, DiBartola SP, Dwulet FE. A unique insertion in the primary structure of bovine amyloid AA protein. J Lab Clin Med 113:67-72, 1989.
Benson MD II, Julien J, Zeldenrust S, Benson MD. A transthyretin varient (alanine 49) associated with familiar amyloidotic polyneuropathy in a French family. J Med Gen 30:117-119, 1993.
Benson MD II, Turpin JC, Lucotte G, Zeldenrust S, LeChevalier B, Benson MD. A transthyretin variant (alanine 71) associated with familiar amyloidotic polyneuropathy in a French family. J Med Gen 30:120-122, 1993.
Xiao G, Wang D, Benson MD, Karsenty G, Franceschi RT. Role of the alpha 2 integrin in osteoblast-specific gene expression and activation of the Osf2 transcripton factor. J Biol Chem 273:32988-94, 1998.
Benson MD*, Aubin JR*, Xiao G, Thomas PE, Franceschi RT. Cloning of a 2.5 kb murine bone sialoprotein promoter fragment and functional analysis of putative Osf2 binding sites. J Bone Miner Res 14:396-405, 1999. * co-first authors
Franceschi RT, Xiao G, Jiang D, Thomas PE, Benson MD. Extracellular matrix regulation of osteoblast-specific gene expression: Role of the α2β1integrin and Osf2/Cbfa1 activation. Proceedings: 6th International Conference on the Chemistry and Biology of Mineralized Tissues, 1999.
Xiao G, Jiang D, Thomas PE, Benson MD, Guan K, Karsenty G, Franceschi RT. MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor Cbfa1. J Biol Chem 275:4453-4459, 2000.
Benson MD, Bargeon JL, Xiao G, Thomas PE, Kim A, Cui Y, Franceschi RT. Identification of a homeodomain binding element in the bone sialoprotein gene promoter that is required for its osteoblast-selective expresion. J Biol Chem 275:13907-13917, 2000.
Xiao G, Gopalakrishnan R, Jiang D, Reith E, Benson MD, Franceschi RT. Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. J Bone Miner Res 17:101-10, 2002.
Gopolakrisnan R., Thomas PE, Benson MD, Wang, D, Franceschi RT. A homeodomain protein element in the bone sialoprotein promoter is critical for tissue-specific expression in bone. Connect Tiss Res 44 (Suppl. 1): 154-160, 2003.
Kuorilehto T, Nissinen M, Koivunen J, Benson MD, Peltonen J. NF1 tumor suppressor protein and mRNA in skeletal tissues of developing and adult normal mouse and NF-1 deficient embryos. J Bone Miner Res 19:983-989, 2004.
Benson MD, Romero MI, Lush ME, Lu QR, Henkemeyer M, Parada LF. Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. Proc Natl Acad Sci USA 102(430): 10694-9, 2005.
Elefteriou F*, Benson MD*, Sowa H*, Starbuck M, Liu J, Ron D, Parada LF, Karsenty G. ATF4 mediation of NF1 pathology in bone reveals a nutritional basis for congenital skeletal dysplasias. Cell Metab 4(6):441-451, 2006 (cover article). *co-first authors
Benson MD, Opperman LA. Regulation of calvarial bone growth by molecules involved in craniosynostoses. Monographs in Human Genetics. Volume 19, Craniosynostoses: Molecular Genetics, Principles of Diagnosis and Treatment. Muenke M, Kress W, Collmann H, Solomon BD, eds., S. Karger, A.G., 2011.
San Miguel S, Serrano MJ, Sachar A, Henkemeyer M, Svoboda KK, Benson MD. Ephrin reverse signaling controls palate fusion via a Pl3 kinase-dependent mechanism. Dev Dyn 240:357-364, 2011.
Benson MD, Serrano MJ. Ephrin regulation of palate development. Front Physiol 3:376, 2012.
Sachar A, Strom TA, Serrano MJ, Benson MD, Opperman LA, Svoboda KK, Liu X. Osteoblasts responses to three-dimensional nanofibrous gelatin scaffolds. J Biomed Mater Res A 100:3029-41, 2012.
- Benson M, Opperman L, Westerlund J, Fernandez C, San Miguel S, Henkemeyer M, Chenaux G. Ephrin B stimulation of calvarial bone growth. Dev Dyn 241:1901-1910, 2012.
- Logan SM, Romero MI, Nguyen DH, Benson MD. Ephrin-B2 expression in the proprioceptive sensory system. Neurosci Lett 545:69-74, 2013.